DoRothEA (Discriminant Regulon Expression Analysis) is a resource that links transcription factors (TFs) with their downstream targets (Garcia-Alonso et al., 2018, 2019). The unity of a TF and its targets is called regulon. The regulons are built from four different strategies:

  1. manually curated interaction repositories
  2. interactions derived from ChIP-seq binding data
  3. in silico predictions of TF binding on gene promoters
  4. reverse-engineered regulons from gene expression datasets.

The TFs activities are computed from gene expression by performing an enrichment analysis (Alvarez et al., 2016), where the regulons are the underlying gene-sets.

The analysis

The selected parameters:

The code:

regulons <- dorothea_regulon %>%
      dplyr::filter(confidence %in% params$selected_conf_level)

dorothea::run_viper(dorothea_matrix, 
                    regulons,
                    options =  list(minsize = minsize,
                                    method = method,
                                    eset.filter = FALSE,
                                    cores = 1,
                                    verbose = FALSE,
                                    nes = TRUE))

The results

The computation yields a matrix with the normalised enrichment scores for each TF across all samples.

The heatmap provides a comprehensive overview of all contrasts/samples. This heatmap includes the top 25 selected TFs for the sample stat compared with the rest of the samples.

The bar plots show the activity of SP1 for all given contrasts/samples; and the top 25 regulated TFs for sample stat.

The interactions of SP1 with its targets is shown in a network plot for sample stat.

Blue nodes indicate that the target is over-expressed and red nodes indicate that the target is down-regulated. The color of the edges represent the effect of the TF on its target (either activation or repression). The number of shown nodes can be changed by the corresponding widget.